Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/204202
Title: | Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages |
Author: | Kim, Hyeyeon Aliar, Kazeera Tharmapalan, Pirashaanthy Mccloskey, Curtis W. Kuttanamkuzhi, Abhijith Grünwald, Barbara T. Palomero, Luis Mahendralingam, Mathepan J. Waas, Matthew Mer, Arvind S. Elliott, Mitchell J. Zhang, Bowen Al-Zahrani, Khalid N. Langille, Ellen R. Parsons, Michael Narala, Swami Hofer, Stefan Waterhouse, Paul D. Hakem, Razqallah Haibe-Kains, Benjamin Kislinger, Thomas Schramek, Daniel Cescon, David W. Pujana, Miquel A. Berman, Hal K. Khokha, Rama |
Keywords: | Càncer de mama Inhibidors enzimàtics Breast cancer Enzyme inhibitors |
Issue Date: | 1-Oct-2023 |
Publisher: | Elsevier BV |
Abstract: | It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2023.113256 |
It is part of: | Cell Reports, 2023, vol. 42, num. 10 |
URI: | http://hdl.handle.net/2445/204202 |
Related resource: | https://doi.org/10.1016/j.celrep.2023.113256 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
PIIS2211124723012688.pdf | 12.79 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License